Opportunistic infection with Crytococcus neoformans is an increasing complication of patients with debilitating conditions and various hematologic malignancies, as well as those on corticosteroid and immunosuppressive therapy. In addition to these patients at risk, disseminated cryptococcosis occurs in as many individuals with apparently uncompromised defenses. The proposed studies are aimed at delineating the host responses crucial for defense against this fungus. The mechanism of pathogenicity of cryptococcosis will be clarified by critical examination of chemotaxis and phagocytosis by both granulocytes and macrophages of various isolates of C. neoformans differing in virulence, lymphocyte proliferation and lymphokine production in response to various mitogens and fungal antigens, and the effect of cryptococcal capsular polysaccharide on these activities. Those yeast factors that potentiate infection will be described. It is anticipated that these findings will lead to improved methods of diagnosis and treatment of cryptococcosis.